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PubMed1997

Secretoneurin-like immunoreactivity in rat sympathetic, enteric and sensory ganglia.

Distribution of secretoneurin-like immunoreactivity (SN-LI) was studied in the rat sympathetic ganglia/adrenal gland, enteric and sensory ganglia by immunohistochemical methods. SN-LI nerve fibers formed basket-like terminals surrounding many of the postganglionic neurons of the superior cervical, stellate, paravertebral chain ganglia, coeliac/superior mesenteric and inferior mesenteric ganglia. Postganglionic neurons of the superior cervical and other sympathetic ganglia exhibited low-to-moderate levels of SN-LI. In all these sympathetic ganglia, clusters of small diameter (< 10 microm) cells, which may correspond to the small intensely fluorescent (SIF) cells, were found to be intensely labeled. Surgical sectioning or ligation of the cervical sympathetic trunk for 7-10 days resulted in a nearly total loss of SN-LI fibers in the superior cervical ganglia, whereas immunoreactivity in the postganglionic neurons and small diameter cells remained essentially unchanged. In the thoracolumbar and sacral segments of the spinal cord, SN-LI nerve fibers were detected in the superficial layers of the dorsal horn as well as in the intermediolateral cell column (ILp). Occasionally, SN-LI somata were noted in the ILp. SN-LI nerve fibers formed a delicate plexus underneath the capsule of the adrenal gland, some of which traversed the adrenal cortex and reached the adrenal medulla. While heavily invested with SN-LI nerve terminals, chromaffin cells seemed to express a low level of SN-LI. In the enteric plexus, varicose SN-LI nerve fibers and terminals formed a pericellular network around many myenteric and submucous ganglion cells; the ganglionic neurons were lightly to moderately labeled. A population of ganglion cells in the dorsal root, nodose and trigeminal ganglia exhibited moderate-to-strong SN-LI. The detection of SN-LI in nerve fibers and somata of various sympathetic ganglia, enteric plexus and adrenal medulla and in somata of the sensory ganglia implies an extensive involvement of this peptide in sympathetic, enteric and sensory signal processing.

Animals↗
PubMed2000

Proceedings of a symposium on the neurobiology of the basal ganglia. Glasgow, United Kingdom, July 1999.

The basal ganglia occupy a commanding place in neuroscience research, in clinical neurology and in biomedical education. The paucity of our understanding of the role of the basal ganglia in normal everyday life combined with our more extensive knowledge of their deficiencies in a variety of clinical syndromes is a potent spur to continuing investigation. That some of these neurodegenerative syndromes-such as Parkinson's disease-are already common only heightens the need for insight in the face of a population with increasing expectations of longevity. About a decade ago an explosion of information on the connectivity and immunocytochemistry of forebrain structures gave rise to concepts which have shaped the fabric of basal ganglia theory-'patch and matrix', 'disinhibition', 'parallel circuits'. Some of these ideas seemed to facilitate an understanding of the basal ganglia, others to render them more complex and impenetrable. Perhaps unsurprisingly, the work of the last decade has tended towards consolidation and refinement. However, several new developments are receiving attention, many of them related to disorders of the basal ganglia. The realisation that some forms of Parkinson's disease have a genetic determinant is gaining strength. The molecular biology of the dopaminergic synapse on the one hand and of the production of insoluble proteins on the other will clearly influence future research into therapeutic options and neuroprotection. The importance of apoptosis, neural plasticity and free radical formation remains unresolved but these are potential areas of promise. Meanwhile, scanning techniques for brain imaging are allowing real time investigation of the working striatum in normal and disordered humans and animals.We believe that the time is opportune for a broad review of current thinking on the basal ganglia in health and disease. The following articles are based on presentations given at a Symposium on the Neurobiology of the Basal Ganglia held at Glasgow University in July 1999 as part of the Summer Meeting of the Anatomical Society of Great Britain and Ireland. The invited speakers were chosen to be wide ranging and contributions encompassed evolution, circuitry and receptors of the basal ganglia, striatal remodelling after dopamine loss, striatal functioning in humans with Huntington's disease and in primate models after midbrain fetal transplants, and the genetics of basal ganglia disorders. Short presentations and posters of current results supplemented the main presentations and some are also included amongst these reviews.

Animals↗
PubMed1989

Preganglionic and sensory origins of calcitonin gene-related peptide-like and substance P-like immunoreactivities in bullfrog sympathetic ganglia.

These experiments further define the organization of peptidergic pathways in the paravertebral sympathetic system of the bullfrog. Populations of axons and synaptic boutons in sympathetic ganglia 9 and 10 were found to express calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) and substance P-like immunoreactivity (SP-IR). CGRP-IR is present in fibers that run through the ganglia and in boutons that make contact with almost half of the principal neurons. SP-IR is also present in fibers within the ganglia and in a rare class of synaptic boutons that are found on less than 1% of the principal neurons. Both forms of immunoreactivity are coexpressed in some nerve fibers and in the rare synaptic boutons that contain SP-IR. Neuropeptide Y-like immunoreactivity (NPY-IR), a marker for C-type postganglionic neurons, was used to identify the postsynaptic targets of boutons containing CGRP-IR and SP-IR. Ninety-five percent of the ganglion cells contacted by CGRP-IR boutons were negative for NPY-IR and are therefore likely to be B-type postganglionic neurons. Similarly, 100% of the ganglion cells contacted by boutons containing SP-IR were negative for NPY-IR. Lesions of the sympathetic chain demonstrated that synaptic boutons containing CGRP-IR arise from neurons whose axons enter the chain rostral to ganglion 7. Cutting the chain between ganglia 8 and 9 eliminates all preganglionic B and C inputs to ganglia 9 and 10. The destruction of the preganglionic C pathway by this lesion was verified by staining ganglia 9 and 10 for luteinizing hormone releasing hormone (LHRH). This lesion also eliminated boutons containing CGRP-IR and drastically reduced the number of ganglionic fibers that stained for CGRP-IR and SP-IR. By contrast, cutting the sympathetic chain between ganglia 6 and 7 spared LHRH-IR in the preganglionic C pathway but still eliminated the boutons that normally express CGRP-IR and reduced the amount of staining for SP-IR. CGRP-IR in the sympathetic ganglia arises from preganglionic and sensory neurons whereas ganglionic SP-IR is purely sensory in origin. In the spinal cord, the preganglionic B and C neurons that innervate ganglia 9 and 10 are located in different segments. In segments that contain preganglionic B cells, but not those that contain C cells, there were 243 +/- 37 (mean +/- SD) neurons in the intermediolateral cell column that express CGRP-IR. However, no cell bodies containing SP-IR were found in this region of the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Calbindin immunoreactivity in sensory and autonomic ganglia in the guinea pig.

Immunoreactivity (IR) for the calcium binding protein, calbindin, was localized in sensory ganglia (nodose, trigeminal and dorsal root), in parasympathetic ganglia (otic and sphenopalatine) in sympathetic chain ganglia and in sympathetic pre-vertebral ganglia of guinea pig. In sensory ganglia, fine nerve fibres with calbindin-IR surrounded the majority of cell bodies, a low proportion of which were themselves reactive. In cranial parasympathetic and in sympathetic chain ganglia, a small proportion of nerve cells was surrounded with baskets of calbindin-IR nerve fibres, but very few cell bodies were reactive. In prevertebral sympathetic ganglia, dense networks of terminals surrounded many cell bodies, but few somata were themselves reactive. In the coeliac and inferior mesenteric ganglia, the calbindin-IR nerve fibres surrounded somatostatin-IR cell bodies, but not those with neuropeptide Y-IR. It is concluded that specific subgroups of peripheral autonomic and sensory neurones have calbindin-IR.

Animals↗
PubMed1992

Localization of herpes simplex virus and varicella zoster virus DNA in human ganglia.

Human dorsal root ganglia from 14 randomly autopsied adults and 1 infant (all seropositive for both herpes simplex virus [HSV] and varicella zoster virus [VZV]) were examined for latent HSV-1 and VZV DNA by polymerase chain reaction. Thoracic ganglionic DNA from all subjects and trigeminal ganglionic DNA from 11 adults were analyzed. HSV-1 DNA was detected in trigeminal ganglia from 8 of 11 (73%) adults and in thoracic ganglia from 2 of 14 (14%) adults. VZV DNA was detected in trigeminal ganglia from 10 of 11 (91%) adults and in thoracic ganglia from 12 of 14 (86%) adults. None of the DNA samples were positive with primers specific for HSV-2. These findings indicate the presence of latent HSV-1 and VZV DNA in trigeminal ganglia and latent VZV DNA in thoracic ganglia of most seropositive adults. Furthermore, although HSV-1 latency most commonly develops in trigeminal ganglia, we also show for the first time the presence of HSV-1 latency in thoracic ganglia. Finally, both viruses can become latent in the same trigeminal ganglion.

Base Sequence↗
PubMed2005

Regional cardiac ganglia projections in the guinea pig heart studied by postmortem DiI tracing.

Our purpose was to identify and localize intrinsic cardiac ganglia innervating distinct regions of the heart using postmortem tracing of nerve projections with DiI, a method not previously used to study the intrinsic cardiac nervous system. We also investigated the possibility of collateral innervation of myocardium and intrinsic ganglia. In isolated paraformaldehyde-fixed guinea pig hearts, crystals of DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) were inserted into the posterior ventricular myocardium below the atrioventricular groove, the right atrium, or the left ventricular septum. Hearts were placed in the dark at 37 degrees C for 2-14 weeks to allow DiI diffusion within neuronal membranes. Labeled neurons were observed in intracardiac ganglia after at least 4 weeks of dye exposure. Labeling was restricted to the inferior-most ganglia (those near the atrioventricular groove) when DiI was inserted into the posterior ventricular myocardium and to ganglia near the sinus node after right atrial DiI placement. Application of DiI to the left ventricular septum resulted in neuron labeling in ganglia primarily in the interatrial septum near the atrioventricular node. After 8 weeks, DiI-labeled nerve fibers and varicosities were seen surrounding unlabeled neurons in some ganglia, suggesting that axons terminating in or passing through the DiI application site in posterior ventricular tissue had collateral branches innervating these ganglia. These results indicate that intrinsic innervation of major cardiac subdivisions is accomplished by regionally segregated cardiac ganglia. Also, tracing with DiI has provided evidence for collateral nerve projections that could be the substrate for novel intracardiac regulatory circuits.

Animals↗
PubMed1984

Size of neurons and glial cells in the enteric ganglia of mice, guinea-pigs, rabbits and sheep.

A quantitative light microscopic study has been carried out on the myenteric and submucosal ganglia of the stomach, duodenum, ileum, proximal colon and rectum of the guinea-pig; the enteric ganglia of the ileum were studied also in the mouse, rabbit and sheep. The area of the profiles of nerve cells, of nerve cell nuclei and of glial nuclei, and the proportion of the area of ganglia occupied by neuropil were measured, and the relative numbers of neurons and glial cells were estimated. The myenteric ganglia were found to be firmly anchored to the stroma of the muscle coat; their shape and the shape of their component cells varied with contraction and distension of the musculature. The range of neuronal sizes in the myenteric ganglia was extremely wide. In the guinea-pig, the myenteric neurons were on average largest in the stomach and duodenum and smallest in the ileum, with intermediate values in the colon and rectum; the submucosal neurons showed little variation in average size along the length of the gut. The average size of ganglion neurons in the ileum was greatest in the sheep and smallest in the mouse, and had intermediate values in the guinea-pig and rabbit. The percentage volume of neuropil in the myenteric ganglia was 51% in the mouse, 65% in the guinea-pig, 70% in the rabbit, and 74% in the sheep. The number of glial cells relative to the number of neurons was also ranked in the same order. In all the species examined the submucosal ganglia, when compared with the corresponding myenteric ganglia, had a smaller percentage volume of neuropil, a much smaller number of glial cells and (except in the mouse ileum) neurons of smaller average size. In all the ganglia there was a positive correlation between size of neurons and size of glial cells. The results are discussed in the light of possible relations between body size (and length of the intestine), numerical density of ganglion neurons, average size of neurons, amount of musculature, average distance between neurons, and amount of neuropil.

Animals↗
PubMed1978

Substance P-like immunoreactivity in cultured spinal ganglia from chick embryos.

The localization of substance P (SP) or a SP-like peptide in cultured ganglia from chick embryos was studied by the indirect immunofluorescence technique. Ganglia from 8-16 days old chick embryos and from newly hatched chickens were cultured in a control medium or in the presence of nerve growth factor (NGF). Addition of colchicine and exposure to different explanted peripheral tissues were also tried. Ganglia from the younger embryos (8-12 days) cultured for 24 h with added NGF showed a weak SP-like immunoreactivity (SPLI) in some cell bodies and strong specific immunofluorescence in nerve fibres growing out from the ganglia. In spinal ganglia of the older embryos (14 and 16 days) and newly hatched chickens cultured with and without NGF the concentration of SPLI in the cell bodies was considerably higher. Addition of colchicine to spinal ganglia cultured 12 h in NGF-medium, resulted in retraction of nerve fibres and strongly fluorescent, expanded nerve fibres were observed in peripheral parts of the ganglia. Explants of skin placed near the spinal ganglia stimulated the outgrowth of fibres, some of them containing SPLI. A few fluorescent fibres were also seen within the skin explants. Also heart tissue explants stimulated outgrowth of nerve fibres, but innervation of these explants with SPLI-containing nerves could not be observed. Nerve fibre-extension from the spinal ganglia was not stimulated by spinal cord explants. The present results support the existence of SP-containing primary sensory neurons in chickens.

Age Factors↗
PubMed1998

Facial nerve parasympathetic preganglionic afferents to the accessory otic ganglia by way of the chorda tympani nerve in the cat.

The distribution of accessory otic ganglia and connections between the ganglia and the chorda tympani nerve were investigated in the cat in order to determine the parasympathetic preganglionic facial nerve afferents to the otic ganglia using whole mount acetylthiocholinesterase (WATChE) histochemistry. The otic ganglia consist of a single main prominent ganglion and many small accessory ganglia lying on a plexus around the origins of the branches of the mandibular nerve and near the junction of the chorda tympani nerve and lingual nerve. In cell analysis of Nissl-stained preparations, the neurons composing the accessory otic ganglia were morphologically similar to the main otic ganglion neurons. Connecting branches from the chorda tympani nerve to the peripherally located accessory otic ganglia were found and they were not stained by WATChE histochemistry. WATChE-positive connecting branches from the ganglia to the inferior alveolar, lingual, and mylohyoid nerves were also found in the same preparations. The WATChE histochemistry on various autonomic nervous tissues revealed that autonomic postganglionic nerve fibers are selectively stained darkly and that preganglionic fibers remain unstained. Therefore, it is considered that the WATChE-negative connections from the chorda tympani nerve consist chiefly of autonomic preganglionic fibers, whereas the WATChE-positive connections to the branches of the mandibular nerve are mainly postganglionic fibers. This suggests that some of the facial nerve parasympathetic preganglionic fibers in the chorda tympani nerve are mediated in the accessory otic ganglia and then join the branches of the mandibular nerve to supply the target mandibular tissues.

Acetylcholinesterase↗
PubMed2006

Immunohistochemical, histochemical and radioassay analysis of nitric oxide synthase immunoreactivity in the lumbar and sacral dorsal root ganglia of the dog.

In this study, immunohistochemistry for neuronal nitric oxide synthase (bNOS-IR), nicotinamide adenine dinucleotide phosphate diaphorase histochemistry (NADPHd) and nitric oxide synthase radioassay were used to study the occurrence, number and distribution pattern of nitric oxide synthesizing neurons in the lumbar (L1-L7) and sacral (S1-S3) dorsal root ganglia of the dog. Nitric oxide synthase immunolabelling was present in a large number of small- (area <1,000 microm(2)) and medium-sized (area 1,000-2,000 microm(2)) as well as in a limited number of large-sized (area >2000 microm(2)) neurons. Although neuronal nitric oxide synthase immunolabelling and histochemical staining provided intense staining of multiple small- and medium-sized neurons in all lumbar and sacral dorsal root ganglia, immuno-labelled or histochemically stained somata exhibited little topographic distribution in individual dorsal root ganglia. Great heterogeneity was noticed in the immunolabelling of medium-sized nitric oxide synthase immunopositive neurons ranging from lightly immuno-labelled somata to heavily immunoreactive ones with completely obscured nuclei. Both staining procedures proved to be highly effective in visualizing intraganglionic fibers of various diameters. In general, the largest fibers revealed at the peripheral end of lumbar and sacral dorsal root ganglia were larger, 6.49-9.35 mum in diameter, while those running centrally and proceeding into the dorsal roots were about 30% reduced, ranging between 5.32 and 8.67 microm in diameter. Peripherally, the occurrence of nitric oxide synthase detected in axonal profiles, and confirmed histochemically, in the specimens of the femoral and sciatic nerves, is the first indication of the presence of nitric oxide synthase in the peripheral processes of somata located in L4-S2 dorsal root ganglia. Large and thin central nitric oxide synthase immunoreactive processes of L1-S3 dorsal root ganglion neurons segregate shortly before entering the spinal cord, the former making a massive medial bundle in the dorsal root accompanied by a slim lateral bundle penetrating Lissauer's tract. Quantitative assessment of the distribution of bNOS-IR and/or NADPHd-stained neurons showed a peculiar pattern in relation to spinal levels. Apparent incongruity was found in the total number of NADPHd-stained versus bNOS-IR neurons, demonstrating a clear prevalence of small bNOS-IR somata in all lumbar ganglia, while medium-sized NADPHd-stained somata clearly prevailed all along the rostrocaudal axis with a peak in L5 ganglion. While the number of small bNOS-IR neurons clearly outnumbered NADPHd-stained and NADPHd-unstained somata in S1-S3 ganglia, an inverse relation appeared comparing the total number of medium-sized NADPHd-stained and NADPHd-unstained somata compared with the number of moderate and intense bNOS-IR neurons. Densitometry of bNOS-IR and NADPHd-stained neurons in lumbar and sacral ganglia revealed two distinct subsets of densitometric profiles, one relating to more often found medium-sized bNOS immuno-labelled and the other, characteristic for moderately bNOS immunoreactive somata of the same cell size. Considerable differences in catalytic nitric oxide synthase activity, determined by conversion of [(3)H]arginine to [(3)H]citrulline were obtained in lumbosacral dorsal root ganglia all along the lumbosacral intumescence, the lowest (0.898+/- 0.2 dpm/min/microg protein) being in the L4 dorsal root ganglion and the highest (4.194+/-0.2 dpm/min/microg protein) in the S2 dorsal root ganglion.

Animals↗
PubMed1986

Anatomy of human extrinsic cardiac nerves and ganglia.

The anatomy of the human extrinsic cardiac nerves and ganglia was reinvestigated because descriptions of human cardiac innervation vary, detailed analyses of subhuman mammalian cardiac innervation reveal considerable similarities among species and the anatomic pattern of cardiac innervation observed in subhuman mammals differs significantly from those described for humans. The presence of a consistent pattern of cardiac innervation in subhuman mammals raised the question as to whether a similar pattern exists in humans. To investigate this, the cervical and thoracic autonomic nerves and ganglia were dissected in 13 embalmed and 10 autopsy cadavers. All major sympathetic cardiopulmonary nerves were found to arise from the stellate ganglia and the caudal halves of the cervical sympathetic trunks below the level of the cricoid cartilage. These sympathetic cardiopulmonary nerves usually consisted of 3 nerves on the right side and 4 on the left. In contrast to widely accepted reports, no sympathetic cardiopulmonary nerves were found to arise from the superior cervical ganglia or the thoracic sympathetic trunks inferior to the stellate ganglia. Parasympathetic cardiopulmonary nerves were found to arise from the recurrent laryngeal nerves and the thoracic vagi immediately distal to them. These nerves interconnected with sympathetic cardiopulmonary nerves anterior and posterior to the main pulmonary artery to form the ventral and dorsal cardiopulmonary plexuses. These plexuses contained relatively large discrete nerves as well as smaller interconnections. Emerging from these plexuses to innervate the ventricles were 3 distinct relatively large cardiac nerves, the right and left coronary cardiac nerves and the left lateral cardiac nerve. In addition to these 3 major nerves, small cardiac nerves arose from the plexuses and the thoracic vagi. Histologic examination of representative dissections confirmed the presence of neural tissue and identified the locations of neuronal cell bodies in these structures. Cell bodies were located in the nodose, superior cervical, middle cervical, stellate and thoracic sympathetic ganglia. The middle cervical ganglia varied in size and number. Neuronal cell bodies were found in the cervical and thoracic sympathetic trunks and in small mediastinal ganglia located along the courses of the cardiopulmonary and cardiac nerves. Marked similarities exist between the anatomy of the cardiopulmonary nerves and ganglia of humans and baboons.

Adult↗
PubMed1980

Development of the multiple molecular forms of acetylcholinesterase in chick paravertebral sympathetic ganglia: an in vivo and in vitro study.

The development of acetylcholinesterase (AChE) activity and the distribution of this enzyme among its multiple forms was studied in both tissue extracts and dissociated cell cultures of chick paravertebral sympathetic ganglia. In agreement with previous findings, total AChE (expressed either per ganglion or per microgram protein) increased in vivo between the time of formation of the paravertebral chain (embryonic day 7; E7) to hatching (E20-E21). After this time, enzyme activity changed much more slowly. Sucrose gradient sedimentation analysis of AChE in ganglia of post-hatching chicks revealed multiple forms of AChE with S values of approximately 6.5, 11 and 19.5. Developmental studies showed that 6.5 S and 11 S forms are present as early as day E7. Much of the pre-hatching increase in total AChE is due to increased levels of the 6.5 S form of the enzyme. By hatching, this form comprised approximately 85-90% of the total AChE activity. In contrast, during the first week after hatching, the activity of the 11 S form increased several-fold while that of the 6.5 S remained approximately unchanged. The 19.5 S form, which is thought to be associated with the synaptic membrane, was not detected prior to day E17 and reached adult levels (2-3% of total AChE activity) by the first week after hatching. Development of AChE was also studied in dissociated cell cultures of embryonic ganglia. Essentially all the AChE activity in such cultures was found to be associated with the neurons. Total AChE activity of cultured E11 ganglia increased in a pattern which was both qualitatively and quantitatively similar to that which occurred in vivol. Furthermore, it was found that development of both the 6.5 and 11 S forms of AChE took place in vitro. In cultures of E8, E11, E15 and E19 ganglia, the distribution of activity between the two forms after various times in vitro was similar to that which was found for in vivo ganglia at an equivalent embryonic stage. Such changes were not affected by the elimination of nonneuronal cells from the cultures. Two aspects of in vitro development, however, differed from that which occurred in vivo. First, an increase in 11 S AChE did not occur at ages equivalent to the first week post-hatching. Second, the 19.5 S form did not develop (even after several weeks) in cultures of E8, E11 and E15 ganglia, nor was this form (which was removed during dissociation of the ganglia) regenerated in cultures of E19 ganglia. Such findings suggest that the pattern of development of AChE and its multiple forms in chick sympathetic neurons is in part intrinsically programmed into these cells at an early stage of development as well as in part regulated by extrinsic signals that these cells receive from their chemical and cellular environment.

Acetylcholinesterase↗
PubMed1988

Immunohistochemical localisation and electrophysiological actions of GABA in prevertebral ganglia in guinea-pig.

Immunohistochemical techniques were used to detect the presence of a GABA-like material in prevertebral sympathetic ganglia in guinea-pigs. Varicose, immunolabelled nerve fibres were observed in close proximity to sympathetic neurones in inferior mesenteric ganglia and coeliac ganglia. Non-varicose, immunolabelled nerve fibres were observed in lumbar colonic nerves and superior coeliac nerves, i.e. in nerve bundles peripheral to prevertebral ganglia. Immunolabelling was also present in neurones in the myenteric plexus and in nerve fibres in the circular muscle of the colon, as shown previously (Hills et al., Neuroscience, 22 (1987) 301-312). However, GABA-like immunoreactivity was not observed in the cell bodies of prevertebral ganglia nor in splanchnic nerves central to prevertebral ganglia. It was concluded from these results that prevertebral ganglia in guinea-pig receive a GABAergic innervation from neurones peripheral to the ganglia, possibly from GABA-containing neurones in the myenteric plexus of the gastrointestinal tract. Intracellular recordings were made from sympathetic neurones in the inferior mesenteric ganglion (IMG). Application of GABA onto the IMG caused a slow depolarisation of sympathetic neurones, during which there was a marked decrease in the input resistance of IMG cells. Application of GABA also depressed excitatory postsynaptic potentials (EPSPs) and action potentials in sympathetic neurones excited by cholinergic nerve fibres in the lumbar colonic nerves. The reversal potential of the GABA-induced slow depolarisation was -37 mV, a value close to the chloride equilibrium potential for sympathetic neurones. The actions of GABA were reversibly reduced by the GABAA antagonist, bicuculline, and were modulated in a predictable manner by substituting chloride ions with methane-sulphonate ions. These results indicated that GABA, and presumably GABAergic nerves in prevertebral ganglia, modulate the excitability of sympathetic neurones by acting on GABAA receptors linked to a chloride ionophore.

Animals↗
PubMed1996

Identifiable Achatina giant neurones: their localizations in ganglia, axonal pathways and pharmacological features.

1. An African giant snail (Achatina fulica Férussac), originally from East Africa, is now found abundantly in tropical and subtropical regions of Asia, including Okinawa in Japan. This is one of the largest land snail species in the world. The Achatina central nervous system is composed of the buccal, cerebral and suboesophageal ganglia. The 37 giant neurones were identified in these ganglia by the series of studies conducted over about 20 years. The identifications were made by the localization of these neurones in the ganglia, their axonal pathways and their pharmacological features. 2. In the left buccal ganglion, the four giant neurones, d-LBAN, d-LBMB, d-LBCN and d-LBPN, were identified. In the left and right cerebral ganglia, d-LCDN, d-RCDN, v-LCDN and v-RCDN were identified. The suboesophageal ganglia are further composed of the left and right parietal, the visceral, the left and right pleural, and the left and right pedal ganglia. In the right parietal ganglion, PON, TAN, TAN-2, TAN-3, RAPN, d-RPLN, BAPN, LPPN, LBPN, LAPN and v-RPLN were identified. In the visceral ganglion, VIN, FAN, INN, d-VLN, v-VLN, v-VAN, LVMN, RVMN and v-VNAN were identified. In the left parietal ganglion, v-LPSN was identified. In the left and right pedal ganglia, LPeNLN, RPeNLN, d-LPeLN, d-LPeCN, d-RPeAN, d-LPeDN, d-LPeMN and d-LPeEN were identified. 3. Of the small molecule compounds tested, dopamine, 5-hydroxytryptamine, GABA, L-glutamic acid, threo- or erythro-beta-hydroxy-L-glutamic acid were effective on the Achatina giant neurones. We suppose that these compounds act as the neurotransmitters for these neurones. 4. Of the neuroactive peptides, achatin-I(Gly-D-Phe-Ala-Asp). APGW-amide(Ala-Pro-Gly-Trp-NH2) and Achatina cardioexcitatory peptide (ACEP-1)(Ser-Gly-Gln-Ser-Trp-Arg-Pro-Gln-Gly-Arg-Phe-NH2) were proposed as neurotransmitters, because these were effective on the Achatina giant neurones and their presence was demonstrated in the Achatina ganglia. Further, myomodulin (Pro-Met-Ser-Met-Leu-Arg-Leu-NH2), buccalin (Gly-Met-Asp-Ser-Leu-Ala-Phe-Ser-Gly-Gly-Leu-NH2), FMRFamide (Phe-Met-Arg-Phe-NH2). [Ser2]-Mytilus inhibitory peptide ([Ser2]-MIP) (Gly-Ser-Pro-Met-Phe-Val-NH2), catch-relaxing peptide (CARP) (Ala-Met-Pro-Met-Leu-Arg-Leu-NH2), oxytocin (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2) and small cardioactive peptideB (SCPB) (Met-Asn-Tyr-Leu-Ala-Phe-Pro-Arg-Met-NH2) could also be neurotransmitters because these peptides were also effective on the Achatina giant neurones, though their presence in the ganglia of this animal has not yet been demonstrated. 5. Calcium current (ICa) was recorded from Achatina giant neurones in the Na(+)-free solution containing K(+)-channel blockers under voltage clamp. The Ca2+ antagonistic effects of brovincamine, verapamil, eperisone, diltiazem, monatepil, etc., were compared using the ICa of the Achatina neurones. 6. Almost all of the mammalian small molecule neurotransmitters were effective on the Achatina giant neurones, suggesting that these compounds are acting on the neurones of a wide variety of animal species. However, the pharmacological features of the Achatina neurone receptors to these compounds were not fully comparable to those of the mammalian receptors. For example, we proposed that beta-hydroxy-L-glutamic acid (either threo- or erythro-) could be an inhibitory neurotransmitter for an Achatina neurone. 7. In contrast, the Achatina giant neurones appear to have no receptor for the mammalian neuroactive peptides, except for oxytocin and Arg-vasotocin. On the other hand, many neuroactive peptides were isolated from invertebrate nervous tissues, including achatin-I, a neuroexcitatory tetrapeptide having a D-phenylalanine residue.

Animals↗
PubMed1997

The connections of the primate subthalamic nucleus: indirect pathways and the open-interconnected scheme of basal ganglia-thalamocortical circuitry.

The current view of basal ganglia organization holds that functionally corresponding subregions of the frontal cortex, basal ganglia and thalamus form several parallel segregated basal ganglia-thalamocortical circuits. In addition, this view states that striatal output reaches the basal ganglia output nuclei (the substantia nigra pars reticulata (SNR) and the internal segment of the globus pallidus (GPi)) via a 'direct' pathway, and via an 'indirect pathway' which traverses the external segment of the globus pallidus (GPe) and the subthalamic nucleus (STN). However, the topographical relationships of GPe and STN, and their topographical relationships with the basal ganglia-thalamocortical circuits are still unclear. The present work reviewed primate data on the topographical organization of STN afferents from GPe, and STN efferents to the pallidum, striatum and SNR, and examined these data with respect to a tripartite (motor, associative and limbic) functional subdivision of the striatum and pallidum. This examination indicated the following. (1) On the basis of its efferent connections, the STN may be divided into a motor and an associative territories, as well as a smaller limbic territory, each projecting to corresponding areas in the pallidum and striatum. (2) Efferents from GPe are in a position to contact subthalamic cells projecting to GPi/SNR, thus providing anatomical support for the existence of indirect pathways. (3) Moreover, given the tripartite division of the striatum, pallidum, and STN, the available data indicate the existence of indirect pathways connecting functionally corresponding subregions of the striatum, pallidum, and STN, as well as indirect pathways connecting functionally non-corresponding subregions. On the basis of the above we suggested that there may be two types of indirect pathways, one which terminates in the same subregion in GPi/SNR as the direct pathway arising from the same striatal subregion, and another which terminates in a different GPi/SNR subregion than the direct pathway arising from the same striatal subregion. We termed the former a 'closed indirect pathway' and the latter an 'open indirect pathway'. The application of these concepts to the surveyed data suggested the existence of three closed indirect pathways, each connecting the corresponding functional (motor, associative, and limbic) regions of the striatum, pallidum, STN, and SNR, as well as of two open indirect pathways, one connecting the associative striatum to the motor subregions of the basal ganglia, and the other connecting the associative striatum to the limbic subregions of the basal ganglia. While the organization of the closed indirect pathways fits the closed segregated arrangement of basal ganglia-thalamocortical circuitry, the organization of the open indirect pathways fits the recently suggested open interconnected scheme of basal ganglia thalamocortical circuitry. The clinical implications of this scheme for Huntington's disease are discussed.

Animals↗
PubMed2000

Basal ganglia and cerebellar loops: motor and cognitive circuits.

The traditional view that the basal ganglia and cerebellum are simply involved in the control of movement has been challenged in recent years. One of the pivotal reasons for this reappraisal has been new information about basal ganglia and cerebellar connections with the cerebral cortex. In essence, recent anatomical studies have revealed that these connections are organized into discrete circuits or 'loops'. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia and cerebellum. The properties of neurons within the basal ganglia or cerebellar components of these circuits resembles the properties of neurons within the cortical areas subserved by these loops. For example, neuronal activity within basal ganglia and cerebellar loops with motor areas of the cerebral cortex is highly correlated with parameters of movement, while neuronal activity within basal ganglia and cerebellar loops with areas of the prefrontal cortex is more related to aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Studies of basal ganglia and cerebellar pathology support this conclusion. Damage to the basal ganglia or cerebellar components of circuits with motor areas of cortex leads to motor symptoms, whereas damage of the subcortical components of circuits with non-motor areas of cortex causes higher-order deficits. In this report, we review some of the new anatomical, physiological and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex.

Animals↗
PubMed1996

The basal ganglia: focused selection and inhibition of competing motor programs.

The basal ganglia comprise several nuclei in the forebrain, diencephalon, and midbrain thought to play a significant role in the control of posture and movement. It is well recognized that people with degenerative diseases of the basal ganglia suffer from rigidly held abnormal body postures, slowing of movement, involuntary movements, or a combination of these a abnormalities. However, it has not been agreed just what the basal ganglia contribute to normal movement. Recent advances in knowledge of the basal ganglia circuitry, activity of basal ganglia neurons during movement, and the effect of basal ganglia lesions have led to a new hypothesis of basal ganglia function. The hypothesis states that the basal ganglia do not generate movements. Instead, when voluntary movement is generated by cerebral cortical and cerebellar mechanisms, the basal ganglia act broadly to inhibit competing motor mechanisms that would otherwise interfere with the desired movement. Simultaneously, inhibition is removed focally from the desired motor mechanisms to allow that movement to proceed. Inability to inhibit competing motor programs results in slow movements, abnormal postures and involuntary muscle activity.

Animals↗
PubMed1998

Involvement of basal ganglia transmitter systems in movement initiation.

The basal ganglia have been implicated in a number of important motor functions, in particular in the initiation of motor responses. According to the current model of basal ganglia functions, motor initiation is supposed to be associated with an inhibition of basal ganglia output structures (substantia nigra pars reticulata/entopeduncular nucleus) which, in turn, might be brought about by corresponding striatal activity changes conveyed via direct and indirect intrinsic pathways to the substantia nigra pars reticulata and the entopeduncular nucleus. Rodent studies using neuropharmacological manipulations of basal ganglia transmitter systems by neurotoxins or drugs provide converging evidence that dopamine within the caudate-putamen, but also within extrastriatal basal ganglia nuclei, is involved in motor initiation by modulating the activity of direct and indirect intrinsic pathways. However, the striatal segregation of dopamine D1 and D2 receptors in control of the direct and indirect projection neurons seems not to be maintained throughout the basal ganglia. In dopamine intact animals, striatal glutamate plays a major role in response initiation probably through actions on striatopallidal neurons involving N-methyl-D-aspartate, but not alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. Striatal adenosine might also contribute to movement initiation by acting on adenosine A2A receptors located on striatopallidal neurons. Analysis of two integral parts of the indirect pathway revealed that inactivation of the subthalamic nucleus was found to facilitate response initiation, while inactivation of the globus pallidus resulted in facilitation as well as inhibition of response initiation indicating a complex contribution of this latter nucleus. Glutamate and gamma-amino-butyric acid (GABA) controlling the activity of the substantia nigra pars reticulata could be involved in control of response initiation in a way predicted by the simplified model of basal ganglia functions. In contrast, the role of the entopeduncular nucleus in response initiation and its control through GABA and glutamate is at variance with this hypothesis, suggesting functional differences of the output structures. Taken together, neurochemical systems of the basal ganglia significantly contribute to intact response initiation by mechanisms which are only partly consistent with predictions of the current functional scheme of the basal ganglia. This suggests that a more complex model is required to account for these disparate findings.

Animals↗